PEPTIDE SPECIFICITY OF ALLOREACTIVE CD4 POSITIVE T-LYMPHOCYTES DIRECTED AGAINST A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I DISPARITY

The mouse strains C57BL/6 (B6, H2(b)) and K-bm1 mutant bm1 have a defi ned difference of three amino acids at position 152, 155, and 156 in t he MHC class I K molecule. This causes a change in the side and the bo ttom of the antigen presenting groove of the K molecule resulting in s trong allogeneic responses in vitro and in vivo. Here we report on the peptide specificity of CD4+ T cells of B6 origin directed against the K-bm1 mutant and speculate on the peptide specificity of CD8+ bm1-spe cific T lymphocytes of B6 origin. Bm1-specific CD4+ T helper cells rec ognized a peptide derived from the K-bm1 molecule encompassing the thr ee mutations, presented by MHC class II molecules on syngeneic cells. The ability of this peptide to bind to MHC class II resulted from amin o acid mutations at positions 155 and 156. Furthermore, the recognitio n of the natural peptide derived from the K-bm1 molecule presented by MHC class II I-A(b) molecules on cells of bm1 origin could be blocked by addition of an MHC class II I-A(b) binding competitor peptide. Thus , due to the mutations in an MHC class I molecule, indirect presentati on via MHC class II molecules and MHC class II-restricted recognition of a peptide derived from such a MHC class I molecule is demonstrable.